Method for synthesizing 6-fluoroindole-3-acetonitrile

Abstract

The invention relates to the synthesis of organic compounds, in particular to a method for synthesizing 6-fluoroindole-3-acetonitrile, which comprises the following steps: step one, synthesis of 6-fluorogramine: blending raw materials of 6-fluoroindole, dimethylamine hydrochloride and paraformaldehyde according to the mol ratio of 1:1-1.5:1-2, mixing the raw materials evenly and then adding the mixture to an organic solvent, stirring continuously the mixture during the reaction, and heating and refluxing the mixture to prepare the 6-fluorogramine for stand by services; and step two, synthesis of the 6-fluoroindole-3-acetonitrile: blending the raw materials of the 6-fluorogramine prepared in the step one and sodium cyanide according to the mol ratio of 1:1-2, mixing the raw materials into the organic solvent, refluxing the mixture and evaporating out the solvent, and extracting an organic layer to obtain the 6-fluoroindole-3-acetonitrile. The method has the advantages that the short synthetic route is short and can be completed in just two steps, the raw materials are readily available, the substitution of the third position of indole is accurate, the control is convenient with low cost, the reaction yield is high, and a prepared high-purity medicament intermediate product is applicable to industrial production.

Description

1. Technical field: [0001] The present invention relates to the synthetic method of compound, especially the synthetic method of the compound used for medicine intermediate. 2. Background technology: [0002] 6-Fluoroindole-3-acetonitrile is a commonly used pharmaceutical intermediate. There is no relevant literature report on the synthesis of this compound in China. The main synthesis method currently adopted in foreign countries according to the U.S. patent (Patent USA 1962 No: 3042685) is: [0003] [0004] That is, the first step is to react 6-fluoroindole with formaldehyde and dimethylamine aqueous solution in the acetic acid system to synthesize 6-fluorodigophylline; the second step is to form a salt by reacting 6-fluoroindole with dimethyl sulfate; Three-step reaction in aqueous cyanide solution to obtain the product 6-fluoroindole-3-acetonitrile. [0005] The deficiencies of this product synthesized by the U.S. patent process have: [0006] 1) The first step rea...

AI Technical Summary

Problems solved by technology

[0006] 1) The first step reaction uses formaldehyde aqueous solution and dimethylamine aqueous solution, which has an unpleasant smell, so the operating environment is poor;

[0007] 2) The second step reaction will use highly toxic chemical dimethyl sulfate, and the consumption is very large, the intermediate obtained is an unstable salt, and the product is sticky and the yield is very low;

[0008] 3) Both the first step and the second step need to be carried out under low temperature conditions, the operation is inconvenient, and the cost of low temperature freezing is high;

[0009] 4) The third step cyanation reaction involves the use of excessive sodium cyanide (5 times equivalent), so a large amount of waste water containing highly toxic cyanide is produced, the cost of waste water treatment is high, and the environmental pressure is high

Images